Sex differences in psychotomimetic-induced behaviours in rats
BEHAVIOURAL BRAIN RESEARCH
Authors: Gogos, Andrea; Kusljic, Snezana; Thwaites, Shane J.; van den Buuse, Maarten
Abstract
Animal model studies using equal numbers of males and females are sparse in psychiatry research. Given the marked sex differences observed in psychiatric disorders, such as schizophrenia, using both males and females in research studies is an important requirement. Thus the aim of this study was to examine sex differences in psychotomimetic-induced behavioural deficits relevant to psychosis. We therefore compared the acute effect of amphetamine or phencyclidine on locomotor activity and prepulse inhibition in adult male and female Sprague-Dawley rats. The results of this study were that: (1) amphetamine-induced distance travelled was greater in female rats than in male rats, (2) phencyclidine -induced locomotor hyperactivity was similar in male and female rats; (3) there were no sex differences in amphetamine-or phencyclidine -induced disruption of prepulse inhibition; (4) male rats had an increased startle response after amphetamine. These findings suggest that sensitivity to amphetamine, but not phencyclidine, differs between male and female rats, and that this sex difference is selective to locomotor hyperactivity and startle, but not prepulse inhibition. This study used two widely-used, validated preclinical assays relevant to psychosis; the results of this study have implications for psychiatry research, particularly for disorders where marked sex differences in onset and symptomology are observed. (C)2017 Elsevier B.V. All rights reserved.
Quercetin Reduces Cortical GABAergic Transmission and Alleviates MK-801-Induced Hyperactivity
EBIOMEDICINE
Authors: Fan, Hui-Ran; Du, Wei-Feng; Zhu, Tao; Wu, Yan-Jiao; Liu, Yan-Mei; Wang, Qi; Wang, Qin; Gu, Xue; Shan, Xingyue; Deng, Shining; Zhu, Tailin; Xu, Tian-Le; Ge, Wei-Hong; Li, Wei-Guang; Li, Fei
Abstract
An imbalance between neuronal excitation and inhibition represents a core feature in multiple neuropsychiatry disorders, necessitating the development of novel strategies to calibrate the excitatory-inhibitory balance of therapeutics. Here we identify a natural compound quercetin that reduces prefrontal cortical GABAergic transmission and alleviates the hyperactivity induced by glutamatergic N-methyl-D-aspartate receptor antagonist MK-801. Quercetin markedly reduced the GABA-activated currents in a noncompetitive manner in cultured cortical neurons, and moderately inhibited spontaneous and electrically-evoked GABAergic inhibitory postsynaptic current in mouse prefrontal cortical slices. Notably, systemic and prefrontal-specific delivery of quercetin reduced basal locomotor activity in addition to alleviated the MK-801-induced hyperactivity. The effects of quercetin were not exclusively dependent on alpha 5-subunit-containing A type GABA receptors (GABA(A)Rs), as viral-mediated, region-specific genetic knockdown of the alpha 5-subunit in prefrontal cortex improved the MK-801-evoked psychotic symptom but reserved the pharmacological responsivity to quercetin. Both interventions together completely normalized the locomotor activity. Together, quercetin as a negative allosteric GABA(A)R modulator exerted antipsychotic activity, facilitating further therapeutic development for the excitatory-inhibitory imbalance disorders. (c) 2018 The Authors. Published by Elsevier B.V.